We extend an ongoing longitudinal adoption study to assess genetic and environmental influences on risk factors for substance use and dependence symptoms at three developmental periods: late adolescence, early adulthood, and independent early adulthood. Using data from computerized diagnostic interviews that are common across the components of the Center, we will test, in conjunction with data from Components 2 and 4, four specific hypotheses that are central to the overarching theme of this center: (1) Vulnerability to drug dependence in adolescence is predominantly a generalized phenomenon, with different substances acting as "alternate forms', and with risk factors becoming more specific in adulthood in the absence of antisocial behavior; (2) Persistent drug use that progresses to regular use, abuse, and dependence is a more heritable phenotype than transient drug use; (3) Individuals with persistent drug use, abuse, and symptoms of dependence are more likely to have comorbid symptoms of other psychiatric disorders, especially Conduct Disorder (CD) and Antisocial Personality Disorder (ASPD); and (4) The genetic link between antisocial behavior and persistent and generalized drug use, abuse, and dependence, is mediated through a constellation of individual characteristics that have been characterized as behavioral disinhibition. By the end of the grant cycle, initial diagnostic interviews of dependence symptoms and comorbid psychopathology will have been obtained from all available adopted and non-adopted probands and their siblings (848 individuals) along with 743 re-interviews in early adulthood, and 365 third interviews in independent early adulthood around age 26. The three multiple assessments allow classification into subject clusters differentiated on the basis of persistence and onset age. These data are used to assess two additional hypotheses specific to this component but related to the center's theme that genetic influences on antisocial and substance dependence problems are greater in life-course persistent individuals:(5) Adoptees whose problem behaviors persist into independent early adulthood are genetically more vulnerable than other adoptees, and (6) Young adults who persist in problem substance use into their later 20s are characterized by higher levels of lifetime antisocial symptoms, higher levels of behavioral disinhibition, and are less likely to have accepted adult social roles than young adults who desist.